Hirota, Yuki

写真a

Affiliation

School of Medicine, Department of Anatomy (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

External Links

 

Research Areas 【 Display / hide

  • Developmental biology

Research Keywords 【 Display / hide

  • 大脳皮質発生

  • 神経細胞移動

Research Themes 【 Display / hide

  • developmental biology of brain, 

    2007.01
    -
    Present

 

Books 【 Display / hide

  • Tumors of the Central Nervous System. Volume 9.

    Hirota Yuki, Springer, 2012.01

    Scope: Proliferation of Neuroblasts in the Adult Brain: Role of Diversin

  • Neurogenesis in the adult brain I: Neurobiology.

    Hirota Yuki, Springer, 2011.01

    Scope: Neuronal migration in the adult brain.

  • Neural Development.

    Hirota Yuki, Springer-Verlag, 1999.01

    Scope: The regulatory mechanisms of neural development: roles of cell-aoutonomous and non-cell-autonomous cues in cell-fate decisions.

Papers 【 Display / hide

  • ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex

    Hirota Yuki

    Cereb Cortex (Cerebral Cortex)  28 ( 1 ) 223 - 235 2018.01

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1460-2199

     View Summary

    © The Author 2016. Published by Oxford University Press. All rights reserved. Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex.

  • Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex

    Hirota Yuki

    Frontiers in Cell and Developmental Biology 5 ( 40 )  2017.04

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2296-634X

  • Roles of Wnt Signaling in the Neurogenic Niche of the Adult Mouse Ventricular-Subventricular Zone

    Hirota, Yuki, Sawada, Masato, Huang, Shih-hui, Ogino, Takashi, Ohata, Shinya, Kubo, Akiharu, Sawamoto, Kazunobu

    NEUROCHEMICAL RESEARCH 41 ( 1-2 ) 222 - 230 2016.02

    Research paper (scientific journal),  ISSN  0364-3190

  • Reelin has a preventive effect on phencyclidine-induced cognitive and sensory-motor gating deficits

    Ishii Kazuhiro, Nagai Taku, Hirota Yuki, Noda Mariko, Nabeshima Toshitaka, Yamada Kiyofumi, Kubo Ken ichiro, Nakajima Kazunori

    Neuroscience Research 96   30 - 36 2015.07

    ISSN  0168-0102

     View Summary

    <p>Reelin has recently attracted attention because of its connection to several neuropsychiatric diseases. We previously reported the finding that prior transplantation of GABAergic neuron precursor cells into the medial prefrontal cortex (mPFC) of mice significantly prevented the induction of cognitive and sensory-motor gating deficits induced by phencyclidine (PCP). The majority of the precursor cells transplanted into the mPFC of the recipient mice differentiated into members of a somatostatin/Reelin-expressing class of GABAergic interneurons. These findings raised the possibility that Reelin secreted by the transplanted cells plays an important role in preventing the deficits induced by PCP. In this study, we investigated whether Reelin itself has a preventive effect on PCP-induced behavioral phenotypes by injecting conditioned medium containing Reelin into the lateral ventricle of the brains of 6- to 7-week-old male mice before administrating PCP. Behavioral analyses showed that the prior Reelin injection had a preventive effect against induction of the cognitive and sensory-motor gating deficits associated with PCP. Moreover, one of the types of Reelin receptor was found to be expressed by neurons in the mPFC. The results of this study point to the Reelin signaling pathway as a candidate target for the pharmacologic treatment of neuropsychiatric diseases.</p>

  • Reelin receptors ApoER2 and VLDLR are expressed in distinct spatiotemporal patterns in developing mouse cerebral cortex

    Hirota Yuki, Kubo Ken ichiro, Katayama Kei ichi, Honda Takao, Fujino Takahiro, Yamamoto Tokuo T., Nakajima Kazunori

    Journal of Comparative Neurology 523 ( 3 ) 463 - 478 2015.02

    ISSN  0021-9967

     View Summary

    <p>In mammalian developing brain, neuronal migration is regulated by a variety of signaling cascades, including Reelin signaling. Reelin is a glycoprotein that is mainly secreted by Cajal-Retzius neurons in the marginal zone, playing essential roles in the formation of the layered neocortex via its receptors, apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR). However, the precise mechanisms by which Reelin signaling controls the neuronal migration process remain unclear. To gain insight into how Reelin signaling controls individual migrating neurons, we generated monoclonal antibodies against ApoER2 and VLDLR and examined the localization of Reelin receptors in the developing mouse cerebral cortex. Immunohistochemical analyses revealed that VLDLR is localized to the distal portion of leading processes in the marginal zone (MZ), whereas ApoER2 is mainly localized to neuronal processes and the cell membranes of multipolar cells in the multipolar cell accumulation zone (MAZ). These different expression patterns may contribute to the distinct actions of Reelin on migrating neurons during both the early and late migratory stages in the developing cerebral cortex. J. Comp. Neurol. 523:463-478, 2015.</p>

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • リーリンシグナルによるニューロン移動停止制御機構

    廣田ゆき, 仲嶋一範.

    第124回日本解剖学会総会全国学術集会, 2019.03, Oral Presentation(general)

  • リーリンシグナルによるニューロン移動停止制御機構

    廣田ゆき, 仲嶋一範.

    第41回日本分子生物学会年会 (横浜) , 2018.11, Symposium, Workshop, Panelist (nomination)

  • 大脳皮質発生におけるリーリンシグナルの機能

    廣田ゆき, 仲嶋一範.

    2018年度生理学研究所研究会「神経発達・再生研究会」, 2018.10, Oral Presentation(guest/special)

  • How does Reelin signaling control the termination of neuronal migration?

    Yuki Hirota, Kazunori Nakajima

    第40回日本生物学的精神医学会・第61回日本神経化学会大会 (神戸) , 2018.09, Oral Presentation(general)

  • ApoER2 controls not only neuronal migration but also termination of migration in the developing cerebral cortex”

    Hirota Yuki

    22nd Biennial Meeting of the International Society for Developmental Neuroscience (Nara) , 2018.05, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 大脳皮質層構造形成を司る糖蛋白質リーリンの受容体VLDLRを介した発生および病態時におけるニューロン移動制御機構

    2018
    -
    2019

    鈴木謙三記念医科学応用研究財団, 平成30年度調査研究助成, 廣田ゆき, Other, Principal Investigator

  • 受容体複合体による皮質ニューロン移動制御機構

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 廣田 ゆき, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 大脳皮質形成における樹状突起伸長を介した移動ニューロン配置決定機構

    2017
    -
    Present

    武田科学振興財団, 2017年度 医学系研究奨励, 廣田ゆき, Principal Investigator

  • 多極性ニューロン移動における中心体制御

    2015.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 廣田 ゆき, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • Molecular mechanisms underlying neuronal migration during neocortical development

    2013.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 廣田 ゆき, Grant-in-Aid for Scientific Research (C), Principal Investigator

     View Summary

    The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, ApoER2 and VLDLR and exerts essential roles in the formation of the mammalian layered neocortex. Here, we we found that the neurons ectopically invaded the MZ and that neuronal migration was disrupted in the intermediate zone in the Apoer2 KO mice. Expression of ApoER2 partially but significantly rescued Apoer2 KO phenotype, suggesting that ApoER2 control migratory behavior of neurons by both cell-autonomous and non-cell-autonomous manners. As for cell-autonomous functions, we found that Rap1/integrin α5 and Akt restored the failure of termination of migration beneath the MZ and neuronal migration in the IZ of Apoer2 KO mice. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing cerebral cortex.

Awards 【 Display / hide

  • 公益信託成茂神経科学研究助成基金平成25年度研究助成

    2013.05, 公益信託成茂神経科学研究助成基金, マウス大脳皮質形成過程におけるリーリンシグナルの移動ニューロンへの作用機序

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • 平成22年度名古屋市立大学医学会賞

    2010.12, 名古屋市立大学医学会, 非筋細胞ミオシンⅡによるマウス上衣細胞絨毛の平面極性制御

    Type of Award: Awards of National Conference, Council and Symposium

 

Courses Taught 【 Display / hide

  • EMBRYOLOGY

    2019

  • ANATOMY

    2019

Courses Previously Taught 【 Display / hide

  • 発生学

    Keio University, 2018, Within own faculty

  • 神経解剖学

    Keio University, 2018, Major subject, Within own faculty

  • 肉眼解剖学

    Keio University, 2018, Major subject, Lecture

  • 発生学

    慶應義塾大学医学部, 2018

  • 神経解剖学

    慶應義塾大学医学部, 2018

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Social Activities 【 Display / hide

  • 慶應義塾大学第40回四谷祭 研究室ツアー

    2017.11
    -
    Present
  • 慶應義塾大学医学部解剖学教室仲嶋研究室オープンラボ

    2017.08
    -
    Present
  • 日本学術振興会ひらめきときめきサイエンスプログラム「脳の中で生まれる神経細胞〜脳のできるしくみと医療への応用〜」(名古屋市立大学医学研究科再生医学分野)

    2010.08
    -
    Present
  • 慶應義塾大学医学部ブリヂストン神経発生・再生学寄附講座 市民公開講座「交通外傷と神経再生」.

    2006.03
    -
    Present

Memberships in Academic Societies 【 Display / hide

  • 日本神経化学会

     
  • 日本神経科学会

     
  • 日本解剖学会

     
  • 日本分子生物学会

     

Committee Experiences 【 Display / hide

  • 2017.07
    -
    Present

    出版・広報委員会, 日本神経化学会